Blocking P-selectin protects from ischemia/reperfusion-induced acute renal failure

Kai Singbartl, Samuel A. Green, Ley Klaus

Research output: Contribution to journalArticle

162 Scopus citations

Abstract

Acute renal failure (ARF) in response to ischemia-reperfusion is thought to be associated with neutrophil infiltration. Neutrophil recruitment depends on adhesion molecules, including P-selectin. Our study sought to characterize the role of P-selectin in ischemia-reperfusion (I/R) -induced acute renal failure (ARF). In wild-type (wt) and P-selectin-deficient (P-/-) mice (both C57BL/6), ARF was induced by 32 min bilateral renal ischemia, followed by reperfusion (I/R). Wt showed a 12- and 20-fold increase in creatinine at 24 and 48 h after I/R, respectively. Similar changes were seen in blood urea nitrogen (BUN). By contrast, in P-/- creatinine and BUN increased only moderately (fourfold over sham). In wt, renal myeloperoxidase activity, indicating neutrophil infiltration, peaked after 24 h (19-fold over sham). This was significantly attenuated in P-/- (fivefold over sham). Western blot analysis revealed maximum P-selectin expression 12 h after I/R in wt. Immunostaining detected P-selectin in glomerular endothelium and in platelets adherent in glomerular and peritubular vessels. Post-ischemic injection of P- selectin antibody at 10 min after reperfusion, but not isotype control antibody, protected wt from ARF similar to the protection seen in P-/-. We conclude that blocking P-selectin even after onset of reperfusion protects mice from I/R-induced ARF, suggesting potential therapeutic strategies aimed at blocking P-selectin.

Original languageEnglish (US)
Pages (from-to)48-54
Number of pages7
JournalFASEB Journal
Volume14
Issue number1
DOIs
StatePublished - 2000

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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